Differential proteomic and phenotypic behaviour of papillary and anaplastic thyroid cell lines

Abstract

Thyroid carcinomas account for a minority of all malignant tumours but, after those of the gonads, they represent the most common forms of endocrine cancers. They include several types, among which the papillary thyroid cancer (PTC) and the anaplastic thyroid cancer (ATC) are the best known. The two hystotypes display significant biological and clinical differences: PTC is a well differentiated form of tumour with a high incidence and a good prognosis, while the ATC is less frequent but represents one of the most aggressive endocrine tumours with morphological features of an undifferentiated type. To date, as far as we know, no conclusive studies, useful to design arrays of molecular markers, have been published illustrating the phenotypic and proteomic differences between these two tumours. The aim of this work was to perform a comparative analysis of two thyroid cancer cell lines, derived respectively from papillary (BCPAP) and anaplastic (8505C) thyroid carcinomas. The comparative analysis included cell behaviour assays and proteomic analysis by 2D-PAGE and mass spectrometry. IntroductionThe human thyroid gland is composed of a basic structural unit, the follicle, consisting of a monolayer of well polarized cells, the thyrocytes, responsible for the T3/T4 hormone secretion, and of other peripheral cells, the parafollicular C cells, responsible for the secretion of calcitonin. The presence within the follicle of stem cells, or remnants of embryonic cells, has been hypothesized as the target cells for tumour initiation. A thin extracellular matrix, which includes occasional fibroblasts and inflammatory cells, is peripheral to the follicle structure. Thyroid carcinomas account for 1-2% of all malignant tumours and, after those of the gonads, they represent the most common tumours of the endocrine system. The thyroid

The cross‐talk between estrogen receptor and peroxisome proliferator‐activated receptor gamma in thyroid cancer

“…This pattern of distribution suggests that the ER genomic pathway and the ER nongenomic pathway may function differentially between PTC and ATC, thus possibly offering some clues regarding the different manifestations of PTC cells and ATC cells in terms of the reciprocal inhibition offered by PPARγ and ERβ. The different responses of PTC and ATC cells to the reciprocal interaction of PPARγ and ERβ are line with recent studies of both forms of thyroid cancers at the mRNA and protein levels, in which mRNA and proteomic signatures of ATC were associated much more closely with a high proliferation rate, epithelial to mesenchymal transition, invasion, dedifferentiation, glycolysis, lactate generation, and chemoresistance …”

“…The different responses of PTC and ATC cells to the reciprocal interaction of PPARg and ERb are line with recent studies of both forms of thyroid cancers at the mRNA and protein levels, in which mRNA and proteomic signatures of ATC were associated much more closely with a high proliferation rate, epithelial to mesenchymal transition, invasion, dedifferentiation, glycolysis, lactate generation, and chemoresistance. [23][24][25] Although we did not observe a direct proteinprotein interaction between ER and PPARg through coimmunoprecipitation experiments (data not shown), an indirect contact or communication between them could not be excluded. ERE, which drives the expression of the vitellogenin A2 gene, can also function as a PPRE to be bound by a PPAR/RXR heterodimer, and such a PPAR/ RXR heterodimer inhibits transactivation by the ER through competition for ERE binding.…”

Molecular Signature of Indeterminate Thyroid Lesions: Current Methods to Improve Fine Needle Aspiration Cytology (FNAC) Diagnosis

“…In the field of thyroid cancer, proteomics has been initially applied on thyroid tissue specimens and cancer cell lines [80,81,82,83,84,85,86,87,88,89], using different techniques such as surface-enhanced laser desorption/ionization-time-of-flight-mass spectrometry (SELDI-TOF-MS), liquid chromatography–mass spectrometry (LC/MS) and MS alone. All these studies ended by identifying specific protein signatures for malignant and benign lesions with a final selection of clusters of proteins with discriminating abilities.…”

Proteomics in thyroid cytopathology: Relevance of MALDI‐imaging in distinguishing malignant from benign lesions

“…In previous studies we have already evaluated the feasibility of applying MALDI-MSI to thyroid specimens and preliminary results showed a good level of reproducibility when applying this technology [10]. In this study, we investigated the possibility of obtaining molecular signatures for both malignant and benign thyroid conditions, such as lymphocytic thyroiditis, hyperplastic (HP) goiter and follicular proliferations, with possible relevance to diagnostic and pathogenetic investigations [5][6][7][8][9][10][11][12].…”